CA3096062A1 - Tablet or composition having n-acyl ethanolamine and cannabinoid - Google Patents
Tablet or composition having n-acyl ethanolamine and cannabinoid Download PDFInfo
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- CA3096062A1 CA3096062A1 CA3096062A CA3096062A CA3096062A1 CA 3096062 A1 CA3096062 A1 CA 3096062A1 CA 3096062 A CA3096062 A CA 3096062A CA 3096062 A CA3096062 A CA 3096062A CA 3096062 A1 CA3096062 A1 CA 3096062A1
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- Prior art keywords
- pain
- cannabinoid
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- tablet
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- 229930003827 cannabinoid Natural products 0.000 title claims abstract description 64
- 239000003557 cannabinoid Substances 0.000 title claims abstract description 64
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- 150000003505 terpenes Chemical class 0.000 claims abstract description 24
- 235000007586 terpenes Nutrition 0.000 claims abstract description 24
- 208000002193 Pain Diseases 0.000 claims description 53
- 229950007031 palmidrol Drugs 0.000 claims description 53
- HXYVTAGFYLMHSO-UHFFFAOYSA-N palmitoyl ethanolamide Chemical compound CCCCCCCCCCCCCCCC(=O)NCCO HXYVTAGFYLMHSO-UHFFFAOYSA-N 0.000 claims description 53
- 239000000693 micelle Substances 0.000 claims description 52
- 239000003826 tablet Substances 0.000 claims description 28
- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Chemical compound CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 claims description 26
- 230000001684 chronic effect Effects 0.000 claims description 15
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 claims description 14
- VYBREYKSZAROCT-UHFFFAOYSA-N alpha-myrcene Natural products CC(=C)CCCC(=C)C=C VYBREYKSZAROCT-UHFFFAOYSA-N 0.000 claims description 13
- 208000008035 Back Pain Diseases 0.000 claims description 12
- SEEZIOZEUUMJME-FOWTUZBSSA-N cannabigerolic acid Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1C(O)=O SEEZIOZEUUMJME-FOWTUZBSSA-N 0.000 claims description 12
- 239000006190 sub-lingual tablet Substances 0.000 claims description 12
- 229940098466 sublingual tablet Drugs 0.000 claims description 12
- SEEZIOZEUUMJME-VBKFSLOCSA-N Cannabigerolic acid Natural products CCCCCC1=CC(O)=C(C\C=C(\C)CCC=C(C)C)C(O)=C1C(O)=O SEEZIOZEUUMJME-VBKFSLOCSA-N 0.000 claims description 11
- 208000008930 Low Back Pain Diseases 0.000 claims description 11
- SEEZIOZEUUMJME-UHFFFAOYSA-N cannabinerolic acid Natural products CCCCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(O)=C1C(O)=O SEEZIOZEUUMJME-UHFFFAOYSA-N 0.000 claims description 11
- 208000004296 neuralgia Diseases 0.000 claims description 11
- 208000021722 neuropathic pain Diseases 0.000 claims description 11
- 208000000094 Chronic Pain Diseases 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 10
- 210000004877 mucosa Anatomy 0.000 claims description 10
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- NPNUFJAVOOONJE-ZIAGYGMSSA-N β-(E)-Caryophyllene Chemical compound C1CC(C)=CCCC(=C)[C@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-ZIAGYGMSSA-N 0.000 claims description 10
- FAMPSKZZVDUYOS-UHFFFAOYSA-N alpha-Caryophyllene Natural products CC1=CCC(C)(C)C=CCC(C)=CCC1 FAMPSKZZVDUYOS-UHFFFAOYSA-N 0.000 claims description 9
- 230000005012 migration Effects 0.000 claims description 9
- 238000013508 migration Methods 0.000 claims description 9
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 claims description 7
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 claims description 7
- 206010028391 Musculoskeletal Pain Diseases 0.000 claims description 7
- 229930007744 linalool Natural products 0.000 claims description 7
- 208000001640 Fibromyalgia Diseases 0.000 claims description 6
- NVEQFIOZRFFVFW-UHFFFAOYSA-N 9-epi-beta-caryophyllene oxide Natural products C=C1CCC2OC2(C)CCC2C(C)(C)CC21 NVEQFIOZRFFVFW-UHFFFAOYSA-N 0.000 claims description 5
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
- 208000005741 Failed Back Surgery Syndrome Diseases 0.000 claims description 5
- 208000016604 Lyme disease Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000000450 Pelvic Pain Diseases 0.000 claims description 5
- 208000004983 Phantom Limb Diseases 0.000 claims description 5
- 206010056238 Phantom pain Diseases 0.000 claims description 5
- 206010057239 Post laminectomy syndrome Diseases 0.000 claims description 5
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 206010069055 Vulvovaginal pain Diseases 0.000 claims description 5
- NPNUFJAVOOONJE-UHFFFAOYSA-N beta-cariophyllene Natural products C1CC(C)=CCCC(=C)C2CC(C)(C)C21 NPNUFJAVOOONJE-UHFFFAOYSA-N 0.000 claims description 5
- 208000003295 carpal tunnel syndrome Diseases 0.000 claims description 5
- 229940117948 caryophyllene Drugs 0.000 claims description 5
- NPNUFJAVOOONJE-UONOGXRCSA-N caryophyllene Natural products C1CC(C)=CCCC(=C)[C@@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-UONOGXRCSA-N 0.000 claims description 5
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 230000000968 intestinal effect Effects 0.000 claims description 5
- 235000001510 limonene Nutrition 0.000 claims description 5
- 229940087305 limonene Drugs 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 208000027232 peripheral nervous system disease Diseases 0.000 claims description 5
- 230000002485 urinary effect Effects 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 description 8
- 241000218236 Cannabis Species 0.000 description 7
- 229960004242 dronabinol Drugs 0.000 description 7
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 6
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 description 6
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 description 5
- 229950011318 cannabidiol Drugs 0.000 description 5
- 229940065144 cannabinoids Drugs 0.000 description 5
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 description 5
- 210000003296 saliva Anatomy 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 4
- -1 cannabavarin Chemical compound 0.000 description 4
- 239000002621 endocannabinoid Substances 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 231100000869 headache Toxicity 0.000 description 3
- 239000005414 inactive ingredient Substances 0.000 description 3
- ZLYNXDIDWUWASO-UHFFFAOYSA-N 6,6,9-trimethyl-3-pentyl-8,10-dihydro-7h-benzo[c]chromene-1,9,10-triol Chemical compound CC1(C)OC2=CC(CCCCC)=CC(O)=C2C2=C1CCC(C)(O)C2O ZLYNXDIDWUWASO-UHFFFAOYSA-N 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- 150000001200 N-acyl ethanolamides Chemical class 0.000 description 2
- 208000007613 Shoulder Pain Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- BXWQUXUDAGDUOS-UHFFFAOYSA-N gamma-humulene Natural products CC1=CCCC(C)(C)C=CC(=C)CCC1 BXWQUXUDAGDUOS-UHFFFAOYSA-N 0.000 description 2
- QBNFBHXQESNSNP-UHFFFAOYSA-N humulene Natural products CC1=CC=CC(C)(C)CC=C(/C)CCC1 QBNFBHXQESNSNP-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- RBEAVAMWZAJWOI-MTOHEIAKSA-N (5as,6s,9r,9ar)-6-methyl-3-pentyl-9-prop-1-en-2-yl-7,8,9,9a-tetrahydro-5ah-dibenzofuran-1,6-diol Chemical compound C1=2C(O)=CC(CCCCC)=CC=2O[C@H]2[C@@H]1[C@H](C(C)=C)CC[C@]2(C)O RBEAVAMWZAJWOI-MTOHEIAKSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- UVOLYTDXHDXWJU-UHFFFAOYSA-N Cannabichromene Chemical compound C1=CC(C)(CCC=C(C)C)OC2=CC(CCCCC)=CC(O)=C21 UVOLYTDXHDXWJU-UHFFFAOYSA-N 0.000 description 1
- UVOLYTDXHDXWJU-NRFANRHFSA-N Cannabichromene Natural products C1=C[C@](C)(CCC=C(C)C)OC2=CC(CCCCC)=CC(O)=C21 UVOLYTDXHDXWJU-NRFANRHFSA-N 0.000 description 1
- VBGLYOIFKLUMQG-UHFFFAOYSA-N Cannabinol Chemical compound C1=C(C)C=C2C3=C(O)C=C(CCCCC)C=C3OC(C)(C)C2=C1 VBGLYOIFKLUMQG-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ORKZJYDOERTGKY-UHFFFAOYSA-N Dihydrocannabichromen Natural products C1CC(C)(CCC=C(C)C)OC2=CC(CCCCC)=CC(O)=C21 ORKZJYDOERTGKY-UHFFFAOYSA-N 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 206010019133 Hangover Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010033425 Pain in extremity Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QXACEHWTBCFNSA-SFQUDFHCSA-N cannabigerol Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-SFQUDFHCSA-N 0.000 description 1
- QXACEHWTBCFNSA-UHFFFAOYSA-N cannabigerol Natural products CCCCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-UHFFFAOYSA-N 0.000 description 1
- 229960003453 cannabinol Drugs 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- HCAWPGARWVBULJ-IAGOWNOFSA-N delta8-THC Chemical compound C1C(C)=CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 HCAWPGARWVBULJ-IAGOWNOFSA-N 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
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- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
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- 210000003127 knee Anatomy 0.000 description 1
- 208000024765 knee pain Diseases 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
A composition includes n-acyl ethanolamine, at least one cannabinoid, and at least one terpene. The composition may be in the form of a tablet.
Description
TABLET OR COMPOSITION HAVING N-ACYL
ETHANOLAMINE AND CANNABINOID
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This disclosure claims priority to United States Provisional Patent Application No. 62/651,775 filed on April 3, 2018.
BACKGROUND
ETHANOLAMINE AND CANNABINOID
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This disclosure claims priority to United States Provisional Patent Application No. 62/651,775 filed on April 3, 2018.
BACKGROUND
[0002] Cannabis is used for medicinal reasons to treat disease or alleviate symptoms. For example, the active chemicals in medicinal cannabis can be delivered into the body through inhalation, ingestion, or topical application. Delivery of medicinal cannabis through mucosal membranes is of particular interest due to rapidity of uptake without the detrimental effects associated with inhalation.
SUMMARY
SUMMARY
[0003] A
composition according to an example of the present disclosure includes n-acyl ethanolamine, at least one cannabinoid, and at least one terpene.
composition according to an example of the present disclosure includes n-acyl ethanolamine, at least one cannabinoid, and at least one terpene.
[0004] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
[0005] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is palmitoylethanolamide.
[0006] In a further embodiment of any of the foregoing embodiments, the at least one cannabinoid includes cannabigerolic acid.
[0007] In a further embodiment of any of the foregoing embodiments, the at least one terpene is selected from the group consisting of myrcene, limonene, caryophyllene, linalool, pinene, and combinations thereof.
[0008] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is palmitoylethanolamide. The at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
[0009] In a further embodiment of any of the foregoing embodiments, including by weight, 1 to 2000 parts of the n-acyl ethanolamine and 1 to 2000 parts of the at least one cannabinoid.
[0010] In a further embodiment of any of the foregoing embodimentsõ including by weight, 10 to 1800 parts of the n-acyl ethanolamine and 1 to 100 parts of the at least one cannabinoid.
[0011] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is in the form of micelles that facilitate transmucosal migration of the cannabinoid across mucosa and capillary blood vessels into bloodstreams in mammals.
[0012] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
[0013] In a further embodiment of any of the foregoing embodiments, clinical activities associated with the administration of a sublingual tablet of the composition include:
chronic and neuropathic pain, inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme's Disease, ALS, urinary pain, and vaginal pain.
chronic and neuropathic pain, inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme's Disease, ALS, urinary pain, and vaginal pain.
[0014] A tablet according to an example of the present disclosure includes one or more excipients, n-acyl ethanolamine, at least one cannabinoid, and at least one terpene.
[0015] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
[0016] In a further embodiment of any of the foregoing embodiments, the at least one cannabinoid includes cannabigerolic acid.
[0017] In a further embodiment of any of the foregoing embodiments, the at least one terpene is selected from the group consisting of myrcene, limonene, caryophyllene, linalool, pinene, and combinations thereof.
[0018] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is palmitoylethanolamide. The at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
[0019] In a further embodiment of any of the foregoing embodiments, including by weight, 10 to 1800 parts of the n-acyl ethanolamine and 1 to 100 parts of the at least one cannabinoid.
[0020] In a further embodiment of any of the foregoing embodiments, the n-acyl ethanolamine is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
[0021] A
sublingual tablet according to an example of the present disclosure includes a compressed powder containing one or more excipients, at least one cannabinoid, at least one terpene, and a transmucosal carrier capable of binding with the at least one cannabinoid for transmucosal migration.
sublingual tablet according to an example of the present disclosure includes a compressed powder containing one or more excipients, at least one cannabinoid, at least one terpene, and a transmucosal carrier capable of binding with the at least one cannabinoid for transmucosal migration.
[0022] In a further embodiment of any of the foregoing embodiments, the transmucosal carrier is in the form of non-oriented molecules.
[0023] In a further embodiment of any of the foregoing embodiments, the transmucosal carrier is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
[0024] In a further embodiment of any of the foregoing embodiments, the transmucosal carrier is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
[0025] In a further embodiment of any of the foregoing embodiments, the transmucosal carrier is palmitoylethanolamide. The at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
[0026] In a further embodiment of any of the foregoing embodiments, the transmucosal carrier is in the form of micelles that facilitate transmucosal migration of the at least one cannabinoid across mucosa and capillary blood vessels into bloodstreams in mammals.
[0027] In a further embodiment of any of the foregoing embodiments, clinical activities associated with the administration of the sublingual tablet include: chronic and neuropathic pain, inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme' s Disease, ALS, urinary pain, and vaginal pain.
BRIEF DESCRIPTION OF THE DRAWINGS
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] The various features and advantages of the present disclosure will become apparent to those skilled in the art from the following detailed description.
The drawings that accompany the detailed description can be briefly described as follows.
The drawings that accompany the detailed description can be briefly described as follows.
[0029] Figure 1 illustrates an example tablet formed of the disclosed composition.
[0030] Figure 2 illustrates a non-oriented form of palmitoylethanolamide.
[0031] Figure 3 illustrates a micelle structure of palmitoylethanolamide.
[0032] Figure 4 illustrates transmigration of micelle across a mucosa.
[0033] Figure 5 illustrates a magnified view of transmigration of micelle along an intra-muco sal pathway.
DETAILED DESCRIPTION
DETAILED DESCRIPTION
[0034] The therapeutic benefit of small molecules originating from cannabis results from the activation of the endocannabinoid system and other non-endocannabinoid receptors and ion channels. The endocannabinoid system includes an extensive array of receptors (CB1 and CB2) and channels (TRP) throughout the peripheral and central nervous system.
Interaction of cannabinoids and their entouragic participants (e.g., terpenes and fatty acid ethanolamides) work together by affecting a homeostatic balance in neurotransmission resulting in therapeutic benefit such as pain relief in particular. The invention operates within this therapeutic realm.
Interaction of cannabinoids and their entouragic participants (e.g., terpenes and fatty acid ethanolamides) work together by affecting a homeostatic balance in neurotransmission resulting in therapeutic benefit such as pain relief in particular. The invention operates within this therapeutic realm.
[0035] Figure 1 schematically illustrates an example tablet 20 for sublingual administration to provide pain relief in humans and other mammals. The tablet 20 is a compressed mixture of one or more powders. It is to be appreciated that the tablet 20 is presented herein to demonstrate a non-limiting example of a composition, which will be described in more detail below, and that the composition may be adapted for other forms of therapeutic administration.
[0036] In particular, sublingual delivery effectiveness depends on the ability of the chemicals being delivered to migrate through the mucosa and capillary blood vessel into the bloodstream. This poses challenges for sublingual delivery of cannabis-based chemicals, which are typically in the form of oils that are practically insoluble in water and have poor migration -- and thus poor sublingual delivery effectiveness. In this regard, as will be appreciated from the present disclosure, the disclosed composition is clinically active in the cannabinoid system of mammals to enhance sublingual migration of cannabis-based chemicals to produce medical benefits in lowering pain.
[0037] The composition of the tablet 20 includes n-acyl ethanolamine 22, at least one cannabinoid 24, and at least one terpene 26. Of these ingredients, the cannabinoid and the n-acyl ethanolamine are active ingredients in the cannabinoid system of mammals, while the terpene is considered to be an inactive ingredient. Depending on the form for medicinal administration of the composition, other inactive ingredients may also be used with the above composition. In the example of the tablet 20, the composition may additionally include excipients or other inactive ingredients. Excipients may be selected to provide desired characteristic release of the active ingredients. As an example, the excipient or excipients may be selected for fast release in the case of sublingual administration.
Excipients for this purpose may include mannitol, polyvinyl alcohol, polyvinypyrrolidone and stearate, but the excipients in general are not limited and may additionally or alternatively include fillers, binders, disintegrants, and lubricants.
Excipients for this purpose may include mannitol, polyvinyl alcohol, polyvinypyrrolidone and stearate, but the excipients in general are not limited and may additionally or alternatively include fillers, binders, disintegrants, and lubricants.
[0038] In examples, the n-acyl ethanolamine is palmitoylethanolamide (PEA), olioylethanolamide (DEA), or a combination thereof. In further examples, the cannabinoid 24 is or includes cannabigerolic acid (CBGA). CBGA is a precursor molecule of other cannabinoids, such as tetrahydrocannabinol (delta-g-tetrahydrocannabinol or delta-8-tetrahydrocannabinol, commonly known as "THC") and cannabidiol (CBD).
Cannabinoids may include, but are not limited to, THC, CBD, cannabinol, cannabavarin, cannabigerol, cannabichromene, c annabicyclol, cannabitriol, cannabielsoin, and non-endogenous cannabinoids. In further examples, the terpene or terpenes can include, but are not limited to, myrcene, limonene, caryophyllene, linalool, and pinene.
Cannabinoids may include, but are not limited to, THC, CBD, cannabinol, cannabavarin, cannabigerol, cannabichromene, c annabicyclol, cannabitriol, cannabielsoin, and non-endogenous cannabinoids. In further examples, the terpene or terpenes can include, but are not limited to, myrcene, limonene, caryophyllene, linalool, and pinene.
[0039] The amounts of the ingredients in the tablet 20 and composition, and in particular the active ingredients, can be selected within pharmaceutically-effective amounts per dose. For example, pharmaceutically-effective amounts are those amounts that clinically reduce pain in mammals. As will be appreciated, due to the enhanced effectiveness of sublingual bioavailability of the disclosed composition, such amounts may differ from effective amounts known for other cannabinoid-containing compositions. In particular, the pharmaceutically-effective amounts of the disclosed composition will be less than effective amounts known for other cannabinoid-containing compositions. Alternatively, it is also contemplated that for equivalent amounts of the disclosed composition to other cannabinoid-containing compositions, the disclosed composition will produce a greater therapeutic effect in reduction of pain due to the enhanced sublingual bioavailability.
[0040] In general, however, the disclosed composition can include, by weight, 1 to 2000 parts of the n-acyl ethanolamine and 1 to 2000 parts of the cannabinoid or combined amount of cannabinoids. As an example, the unitary part by weight is 1 milligram. In further examples, the composition includes 10 to 1800 parts of the n-acyl ethanolamine and 1 to 100 parts of the cannabinoid or combined amount of cannabinoids. In one example, a tablet includes milligrams of CBD, 100 milligrams of PEA, and 0.1 milligrams of terpenes (myrcene, linalool, B caryophylline, and humulene).
[0041] The n-acyl ethanolamine, for example the PEA, can exist in at least two structural configurations, either of which or both of which can be used in the composition. One of these configurations is in the form of non-oriented molecules, an example of which is shown at 28 in Figure 2. The other of these configurations is in the form of micelles, an example of which is shown at 30 in Figure 3.
[0042] The n-acyl ethanolamine or PEA is generally insoluble in water. However, when placed in an aqueous environment, the n-acyl ethanolamine or PEA
molecules self-assemble into micelles. A micelle is an aggregate of molecules that is usually spherical. In the aggregate, the hydrophilic heads of the molecules face outwards from the center of the sphere, while the hydrophobic tails face inwards toward the center of the micelle. For PEA, the hydrophilic heads comprise the alcohol moieties and the hydrophobic tails comprise the fatty acid moieties. In the micelle form, the PEA is water soluble.
molecules self-assemble into micelles. A micelle is an aggregate of molecules that is usually spherical. In the aggregate, the hydrophilic heads of the molecules face outwards from the center of the sphere, while the hydrophobic tails face inwards toward the center of the micelle. For PEA, the hydrophilic heads comprise the alcohol moieties and the hydrophobic tails comprise the fatty acid moieties. In the micelle form, the PEA is water soluble.
[0043] In one example, the disclosed composition includes the n-acyl ethanolamine or PEA in the form of the non-oriented molecules. In this case, when the n-acyl ethanolamine or PEA is exposed to an aqueous environment, such as sublingual saliva, the n-acyl ethanolamine or PEA activates to self-assemble into the micelles. That is, the n-acyl ethanolamine or PEA seeks to achieve a lower energy state in situ.
[0044]
Additionally or alternatively, the composition includes, prior to therapeutic administration, the n-acyl ethanolamine or PEA preassembled in the micelle form. For example, prior to incorporation into the composition, the n-acyl ethanolamine or PEA is mixed into an aqueous solution and optionally agitated. The concentration of the solution may be varied but in one non-limiting example, the aqueous solution may have a concentration of approximately 10 g/L of the n-acyl ethanolamine or PEA in water. The agitation may include sonication. For example, the resulting product is an aqueous n-acyl ethanolamine or PEA
emulsion in which particle size may range from about 0.1 micrometers to 1 micrometer. The emulsion can then be filtered and the filtrate then lyophilized to yield a powder containing dry n-acyl ethanolamine or PEA micelles. The dry n-acyl ethanolamine or PEA
micelles can then be incorporated into the composition. In this example, the n-acyl ethanolamine or PEA would be released into the saliva in a form that is already water soluble, which may facilitate increasing the rate of delivery. That is, the self-assembly step of forming the micelle as with the non-oriented molecules is eliminated by using preassembled n-acyl ethanolamine or PEA
micelles.
Additionally or alternatively, the composition includes, prior to therapeutic administration, the n-acyl ethanolamine or PEA preassembled in the micelle form. For example, prior to incorporation into the composition, the n-acyl ethanolamine or PEA is mixed into an aqueous solution and optionally agitated. The concentration of the solution may be varied but in one non-limiting example, the aqueous solution may have a concentration of approximately 10 g/L of the n-acyl ethanolamine or PEA in water. The agitation may include sonication. For example, the resulting product is an aqueous n-acyl ethanolamine or PEA
emulsion in which particle size may range from about 0.1 micrometers to 1 micrometer. The emulsion can then be filtered and the filtrate then lyophilized to yield a powder containing dry n-acyl ethanolamine or PEA micelles. The dry n-acyl ethanolamine or PEA
micelles can then be incorporated into the composition. In this example, the n-acyl ethanolamine or PEA would be released into the saliva in a form that is already water soluble, which may facilitate increasing the rate of delivery. That is, the self-assembly step of forming the micelle as with the non-oriented molecules is eliminated by using preassembled n-acyl ethanolamine or PEA
micelles.
[0045] The micelles also facilitate transmucosal migration of the cannabinoid. For example, the n-acyl ethanolamine or PEA in the non-oriented molecule form can be exposed to an aqueous environment that also includes the cannabinoid 24. The micelles thus assemble in the presence of the cannabinoid 24 and, as also shown in Figure 3, the cannabinoid 24 thereby becomes incorporated into the micelle 30. In this regard, the n-acyl ethanolamine or PEA serves as a carrier of the cannabinoid 24.
[0046] The n-acyl ethanolamine or PEA is bound with the cannabinoid 24. The binding between the n-acyl ethanolamine or PEA and the cannabinoid 24 is not chemical bonding in the sense of ionic or covalent bonding. Rather, the aggregate of the n-acyl ethanolamine or PEA molecules in the micelle structure physically entraps the cannabinoid 24 molecules, although there may be secondary bonding. In this case, the cannabinoid 24 is hydrophobic and is "packaged" in the hydrophobic interior pocket of the micelle. This occurs spontaneously at standard temperature and pressure via self-assembly by thermodynamic considerations. If preassembled micelle are used in the composition, such entrapment may be conducted prior to therapeutic administration, during the preassembly of the n-acyl ethanolamine or PEA into the micelle form by adding the cannabinoid 24 to the mixture. If the non-oriented n-acyl ethanolamine or PEA is used in the composition, the entrapment may occur in vivo in the saliva during administration. As an example based on preassembled micelle, 100 mg of PEA may be included in a tablet. The 100 mg of PEA is preassembled into the micelle in the presence of 10 mg of THC prior to formation of the tablet. The 10 mg of THC
incorporates into the 100 mg of PET micelles. The final tablet thus contains 10 mg of THC per 100 mg of PEA micelle as a lyophilized powder, which may be a component of a 250 mg tablet.
incorporates into the 100 mg of PET micelles. The final tablet thus contains 10 mg of THC per 100 mg of PEA micelle as a lyophilized powder, which may be a component of a 250 mg tablet.
[0047]
Depending on the concentration of the n-acyl ethanolamine or PEA in an aqueous environment, the equilibrium between the non-oriented molecule form and the micelle form may favor the insoluble non-oriented molecule form. However, in vivo, as the concentration of the micelles are depleted by removal from an aqueous matrix (e.g. saliva) through tissue absorption, the equilibrium may favor conversion of the insoluble form. Thus, over time, the insoluble form will also deplete in the absence of other mechanisms (metabolism).
Depending on the concentration of the n-acyl ethanolamine or PEA in an aqueous environment, the equilibrium between the non-oriented molecule form and the micelle form may favor the insoluble non-oriented molecule form. However, in vivo, as the concentration of the micelles are depleted by removal from an aqueous matrix (e.g. saliva) through tissue absorption, the equilibrium may favor conversion of the insoluble form. Thus, over time, the insoluble form will also deplete in the absence of other mechanisms (metabolism).
[0048] The therapeutic administration of the tablet 20 or composition may include placement into a sublingual space of a mammal. This results in dissolution of the composition into the sublingual space. During dissolution the active ingredients are released from the tablet 20 or composition. If the n-acyl ethanolamine or PEA is in the non-oriented molecule form, the n-acyl ethanolamine or PEA self-assembles into the micelle structure upon release. If the n-acyl ethanolamine or PEA are provided preassembled in micelles, the micelles are released intact into the saliva.
[0049] Figure 4 illustrates an example of transmigration of the micelles 30 (which may include the cannabinoid 24) across a mucosa 32. The micelle 30 begin in an extra-mucosa space 34 and transmigrate along an intra-mucosa pathway 36 through tight junctions of the mucosa cell lining toward a capillary bed 38. Figure 5 illustrates the transmigration of the micelles 30 along the intra-mucosa pathway 36 between lipid bilayers of mucosa cells.
Transmigration is facilitated by the flexibility of the micelle 30, which can change shape to accommodate variation the topography of the pathway 36. The transmigration is facilitated by the polar head groups of the micelle, which interact with the polar head groups of the lipid bilayer of cells. In this manner, the n-acyl ethanolamine or PEA, especially in micelle form, facilitates the water solubility and transport of the cannabinoid 24 across the mucosa. In this manner cannabis delivery to the bloodstream in mammals is facilitated by micellar PEA when administered sublingually. A synergistic affect is thereby realized at reduced concentrations.
Transmigration is facilitated by the flexibility of the micelle 30, which can change shape to accommodate variation the topography of the pathway 36. The transmigration is facilitated by the polar head groups of the micelle, which interact with the polar head groups of the lipid bilayer of cells. In this manner, the n-acyl ethanolamine or PEA, especially in micelle form, facilitates the water solubility and transport of the cannabinoid 24 across the mucosa. In this manner cannabis delivery to the bloodstream in mammals is facilitated by micellar PEA when administered sublingually. A synergistic affect is thereby realized at reduced concentrations.
[0050] STUDY
[0051] A clinical trial was conducted using an example of the disclosed composition for 16 patients ranging in age from 20 to 87, both male and female. Pain scale scores ranged from a 3-8 prior to taking our tablets. Inclusion criteria were mild to moderate pain that was not currently being treated, to avoid overlap of medications.
Any patient taking concomitant pain medication were disqualified from the trial. Tablet composition included: 10 mg CBD, 100 mg PEA, 0.1 mg terpenes: myrcene, linalool, B caryophylline, and humulene.
Any patient taking concomitant pain medication were disqualified from the trial. Tablet composition included: 10 mg CBD, 100 mg PEA, 0.1 mg terpenes: myrcene, linalool, B caryophylline, and humulene.
[0052] Patients were provided with instructions and a diary. They were instructed to assess and document their pain on a pain scale score of 0-10 using VAS
(visual analog scale) and Wong-Baker Faces Pain Rating Scale to help with the VAS scoring:
(visual analog scale) and Wong-Baker Faces Pain Rating Scale to help with the VAS scoring:
[0053] 1. At the onset of pain, initially take one-half of a tablet and place it under your tongue. The tablet will dissolve rapidly in about 60 seconds or less. The patient may swallow normally, but do not eat or drink anything for 3-5 minutes post dose.
[0054] 2. Record the date, time, dose, and initial pain score using the patient diary form.
[0055] 3. After 20 minutes, note the pain score and record in the patient diary.
[0056] 4. Repeat the pain assessment and record score at 40, 60, and 120 minutes.
[0057] 5. If after 20 minutes, there is not pain relief or not completely relieved, take the second 1/2 tablet and repeat instructions in Step 1.
[0058] 6. If the pain is persistent, you may continue to dose, as needed, but not to exceed 3 whole tablets in a 24 hour period. If additional dosing is required, follow the sequence of steps above and record in the patient diary. Measurement parameters: VAS
scores, patient reports of pre and post treatment pain. Patients were encouraged to take notes to describe pre and post treatment pain and how it would compare with their usual treatment.
scores, patient reports of pre and post treatment pain. Patients were encouraged to take notes to describe pre and post treatment pain and how it would compare with their usual treatment.
[0059] Outcomes:
[0060] Patient 1: Female, 56 chronic neuropathic pain
[0061] Time: 0 20 40 60 120
[0062] PSS: 6 2 2 1 1
[0063] Patient 2: Female 63, acute low back pain
[0064] Time: 0 20 40 60 120
[0065] PSS: 4 3 (1/2 tab) 0 0 0
[0066] Patient 3: Male 87 chronic 5 feet, knees, pain
[0067] Time: 0 20 40 60 120
[0068] PSS: 6 4 3 2 0
[0069] Patient 4: Male 32 low back pain
[0070] Time: 0 20 40 60 120
[0071] PSS: 52000
[0072] Patient 5: Female 42 low back and hip pain
[0073] Time: 0 20 40 60 120
[0074] PSS: 6 3 3(1/2 tab) 11
[0075] Patient 6: Male. 32 chronic leg/knee pain
[0076] Time: 0 20 40 60 120
[0077] PSS: 5 2 2 (1/2 tablet) 0 0
[0078] Patient 7: Male 57 chronic foot pain
[0079] Time: 0 20 40 60 120
[0080] PSS: 60000
[0081] Patient 8: Female 23 dysmenorrhea
[0082] Time: 0 20 40 60 120
[0083] PSS 31000
[0084] Patient 9: Female 5 25 low back pain
[0085] Time: 0 20 40 60 120
[0086] PSS: 6 2 2 (1/2 tab) 0 0
[0087] Patient 10: Male 48 chronic low back pain, shoulder pain
[0088] Time: 0 20 40 60 120
[0089] PSS: 6 3 3(1/2 tab) 0 0
[0090] Patient 11: Female 63 headache (hangover)
[0091] Time: 0 20 40 60 120
[0092] PSS 4 2 (1/2 tab) 0 0 0
[0093] Patient 12: Male 48, tooth pain after tooth surgery
[0094] Time: 0 20 40 60 120
[0095] PSS: 8 5 4(1/2 tab) 2 2
[0096] Patient 13: Female 56 Shoulder pain
[0097] Time: 0 20 40 60 120
[0098] PSS: 6 1 0 00
[0099] Patient 14: Female 56 headache, low back pain
[00100] Time: 0 20 40 60 120
[00101] PSS: 4 0 0 0 0
[00102] Patient 15: Female 20 headache
[00103] Time: 0 20 40 60 120
[00104] PSS: 3 0 0 0 0
[00105] Patient 16: Female 63 Fibromyalgia, neck, upper back pain
[00106] Time: 0 20 40 60 120
[00107] PSS: 4 2 (1/2 tab) 11 0
[00108] Study Summary:
[00109] Average age 53.2
[00110] 10 females
[00111] 6 males
[00112] Average starting VAS score= 5.1
[00113] Average pain score 20 mins= 2.0
[00114] Average pain score 40 mins = 1.25
[00115] Average pain score 60 mins=0.43
[00116] Average pain score 120 mins=0.25
[00117] In summary, indications include but are not limited to: chronic and neuropathic pain and inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme's Disease, ALS, urinary pain, and vaginal pain and is neuroprotective.
[00118] Although a combination of features is shown in the illustrated examples, not all of them need to be combined to realize the benefits of various embodiments of this disclosure. In other words, a system designed according to an embodiment of this disclosure will not necessarily include all of the features shown in any one of the Figures or all of the portions schematically shown in the Figures. Moreover, selected features of one example embodiment may be combined with selected features of other example embodiments.
[00119] The preceding description is exemplary rather than limiting in nature.
Variations and modifications to the disclosed examples may become apparent to those skilled in the art that do not necessarily depart from this disclosure. The scope of legal protection given to this disclosure can only be determined by studying the following claims.
Variations and modifications to the disclosed examples may become apparent to those skilled in the art that do not necessarily depart from this disclosure. The scope of legal protection given to this disclosure can only be determined by studying the following claims.
Claims (25)
1. A composition comprising:
n-acyl ethanolamine;
at least one cannabinoid; and at least one terpene.
n-acyl ethanolamine;
at least one cannabinoid; and at least one terpene.
2. The composition as recited in claim 1, wherein the n-acyl ethanolamine is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
3. The composition as recited in claim 1, wherein the n-acyl ethanolamine is palmitoylethanolamide.
4. The composition as recited in claim 1, wherein the at least one cannabinoid includes cannabigerolic acid.
5. The composition as recited in claim 1, wherein the at least one terpene is selected from the group consisting of myrcene, limonene, caryophyllene, linalool, pinene, and combinations thereof.
6. The composition as recited in claim 1, wherein the n-acyl ethanolamine is palmitoylethanolamide, the at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
7. The composition as recited in claim 1, including by weight, 1 to 2000 parts of the n-acyl ethanolamine and 1 to 2000 parts of the at least one cannabinoid.
8. The composition as recited in claim 1, including by weight, 10 to 1800 parts of the n-acyl ethanolamine and 1 to 100 parts of the at least one cannabinoid.
9. The composition as recited in claim 1, wherein the n-acyl ethanolamine is in the form of micelles that facilitate transmucosal migration of the cannabinoid across mucosa and capillary blood vessels into bloodstreams in mammals.
10. The composition as recited in claim 1, wherein the n-acyl ethanolamine is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
11. The composition as recited in claim 1, wherein clinical activities associated with the administration of a sublingual tablet of the composition include: chronic and neuropathic pain, inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme' s Disease, ALS, urinary pain, and vaginal pain.
12. A tablet comprising:
one or more excipients;
n-acyl ethanolamine;
at least one cannabinoid; and at least one terpene.
one or more excipients;
n-acyl ethanolamine;
at least one cannabinoid; and at least one terpene.
13. The tablet as recited in claim 10, wherein the n-acyl ethanolamine is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
14. The tablet as recited in claim 10, wherein the at least one cannabinoid includes cannabigerolic acid.
15. The tablet as recited in claim 10, wherein the at least one terpene is selected from the group consisting of myrcene, limonene, caryophyllene, linalool, pinene, and combinations thereof.
16. The tablet as recited in claim 10, wherein the n-acyl ethanolamine is palmitoylethanolamide, the at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
17. The tablet as recited in claim 10, including by weight, 10 to 1800 parts of the n-acyl ethanolamine and 1 to 100 parts of the at least one cannabinoid.
18. The tablet as recited in claim 10, wherein the n-acyl ethanolamine is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
19. A sublingual tablet comprising:
a compressed powder containing one or more excipients, at least one cannabinoid, at least one terpene, and a transmucosal carrier capable of binding with the at least one cannabinoid for transmucosal migration.
a compressed powder containing one or more excipients, at least one cannabinoid, at least one terpene, and a transmucosal carrier capable of binding with the at least one cannabinoid for transmucosal migration.
20. The sublingual tablet as recited in claim 19, wherein the transmucosal carrier is in the form of non-oriented molecules.
21. The sublingual tablet as recited in claim 19, wherein the transmucosal carrier is in the form of micelles, and the at least one cannabinoid is entrapped in the micelles.
22. The sublingual tablet as recited in claim 19, wherein the transmucosal carrier is selected from the group consisting of olioylethanolamide, palmitoylethanolamide, and combinations thereof.
23. The sublingual tablet as recited in claim 19, wherein the transmucosal carrier is palmitoylethanolamide, the at least one cannabinoid includes cannabigerolic acid, and the at least one terpene includes myrcene.
24. The sublingual tablet as recited in claim 19, wherein the transmucosal carrier is in the form of micelles that facilitate transmucosal migration of the at least one cannabinoid across mucosa and capillary blood vessels into bloodstreams in mammals.
25. The sublingual tablet as recited in claim 19, wherein clinical activities associated with the administration of the sublingual tablet include: chronic and neuropathic pain, inflammation, including peripheral neuropathies such as diabetic neuropathy, chemotherapy induced peripheral neuropathy, carpal tunnel syndrome, phantom limb pain, sciatic pain, osteoarthritis, low back pain, musculo-skeletal pain, failed back surgery syndrome, fibromyalgia, dental pain, post-stroke neuropathic pain, pain from multiple sclerosis, chronic pelvic pain, intestinal inflammation, migraine, cerebral ischemia, complex regional pain syndrome, postherpetic neuralgia, chronic pain from Lyme' s Disease, ALS, urinary pain, and vaginal pain.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP (1) | EP3773512A4 (en) |
CA (1) | CA3096062A1 (en) |
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WO (1) | WO2019195355A1 (en) |
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WO2022162711A1 (en) * | 2021-01-28 | 2022-08-04 | Specchiasol S.R.L. | Composition for the treatment of painful and/or inflammatory states |
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AU2014347807A1 (en) | 2013-10-31 | 2016-05-26 | Full Spectrum Laboratories, Ltd. | Terpene and cannabinoid formulations |
US9044390B1 (en) * | 2014-04-17 | 2015-06-02 | Gary J. Speier | Pharmaceutical composition and method of manufacturing |
US20160039591A1 (en) * | 2014-07-22 | 2016-02-11 | Craig E. Kinzer | Packaging systems, devices, methods, and composition including cannabinoid unit dose forms |
DK3288553T3 (en) * | 2015-04-29 | 2023-01-23 | Scisparc Ltd | COMBINATIONS OF CANNABINOIDS AND N-ACYLETHANOLAMINES |
US11166912B2 (en) * | 2016-03-03 | 2021-11-09 | Ctt Pharma Inc. | Orally administrable composition |
US9833408B1 (en) * | 2016-07-28 | 2017-12-05 | Allen Greenspoon | Orally administrable formulation |
WO2019136351A1 (en) * | 2018-01-05 | 2019-07-11 | Altus Labs, Llc | Personal care compositions |
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- 2019-04-03 US US17/044,521 patent/US11951086B2/en active Active
- 2019-04-03 EP EP19781930.3A patent/EP3773512A4/en active Pending
- 2019-04-03 CA CA3096062A patent/CA3096062A1/en active Pending
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EP3773512A4 (en) | 2021-12-29 |
WO2019195355A1 (en) | 2019-10-10 |
MX2020010424A (en) | 2021-01-15 |
EP3773512A1 (en) | 2021-02-17 |
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